# Decellularized cartilage and progenitor cells for laryngotracheal reconstruction

> **NIH NIH R56** · CHILDREN'S HOSP OF PHILADELPHIA · 2022 · $616,673

## Abstract

PROJECT SUMMARY/ABSTRACTS
Severe subglottic stenosis, the narrowing of the airway just below the vocal folds, develops as a response to
intubation in close to 10% of the > 20,000 premature births per year in the United States. Severe cases require
laryngotracheal reconstruction (LTR), in which surgeons split the cricoid and add a piece of autologous patient-
derived cartilage to expand the airway and restore proper airflow. However, in children, the success rate is as
low as 50% with a high incidence of restenosis requiring revision surgery. Graft failure is tied directly to the lack
of sufficiently sized autologous cartilage in the child, and tissue engineering has been proposed to develop
alterative grafting options for pediatric LTR. Some approaches, including some of our previous work, have
been effective in producing functional cartilage, but the overall timeframe required for the construct to match
the mechanical properties of native cartilage (>24 weeks) is not compatible with clinical translation (<8 weeks).
Furthermore, current cell sources such as expanded autologous chondrocytes and mesenchymal stem cells
frequently result in hypertrophic and calcified tissue. Our objective is to engineer a new type of cartilage
implant that is populated with patients’ cells, mechanically viable and suitable for LTR within a clinically
relevant timeframe. Our approach is to exploit the blood vessels and elastin fibers that are uniquely present in
the fibro-elastic cartilage of the meniscus to form microchannels for effective recellularization after enzymatic
decellularization. Our patent-pending Meniscal Decellularized scaffold (MEND) technology can indeed be
easily recellularized and has mechanical properties of the same order as native tracheal cartilage.
Furthermore, cartilage progenitor cells have been proposed as a rapidly proliferating, highly chondrogenic cell
source. To harness these cells, we have developed a minimally invasive biopsy procedure to harvest ear
Cartilage Progenitor Cells (eCPCs). Our overarching hypothesis is that MEND and eCPCs can be combined to
create cartilage implants with suitable mechanical strength, dimensions, and phenotypic stability for
personalized, minimally invasive LTR. We propose to use MEND recellularized with eCPCs to engineer
cartilage with tissue properties matching those of native cartilage. We will then validate the MEND-engineered
cartilage in a miniature pig LTR model. We expect that our findings will provide strong pre-clinical evidence of
functional laryngotracheal cartilage repair by our innovative eCPC-MEND technology and will thereby prompt
follow up long term studies to eventually apply this technology to restore children’s airway.

## Key facts

- **NIH application ID:** 10704303
- **Project number:** 1R56HL164536-01
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Riccardo Gottardi
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $616,673
- **Award type:** 1
- **Project period:** 2022-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10704303

## Citation

> US National Institutes of Health, RePORTER application 10704303, Decellularized cartilage and progenitor cells for laryngotracheal reconstruction (1R56HL164536-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10704303. Licensed CC0.

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